Naming of a disease or an entity, although seemingly simple, has far-reaching consequences. There have been several attempts to systematize the nomenclature of diseases.97 Best practice recommendations have also been issued by the World Health Organization in this regard for infectious diseases.6 The idea behind these is to impress upon members of the medical fraternity as well as the general populace about the significance of the disease entity. The term ‘non-alcoholic fatty liver disease (acronym-NAFLD)’ encompasses those individuals who have fatty liver without history of significant alcohol intake and other conditions that could cause fatty liver. Importantly, not all patients in Ludwig’s study were overweight/obese. Further research has only consolidated the point that NAFLD is a disease of multifactorial and competing etiologies and can not be ascribed to any single factor.
It has not been possible as of yet to ascribe hepatic steatosis to any single cause and the unitary treatment targeting has not yielded successful treatment options. The general idea is that NAFLD is a spectrum of disorders, with MS occupying a predominant part of that spectrum. Despite years of research, we have not been able to add much to the treatment arsenal of NAFLD. Changing the nomenclature could put an exaggerated emphasis on MS, which ultimately may not turn out to be the only target. While the pathophysiology is still a puzzle, how would a mere change in name help?
MAFLD: Is the new terminology justified?
There have been several arguments put forward by the proponents of MAFLD in favor of a name change. The objections to NAFLD are that NAFLD should be defined by inclusion rather than by exclusion, the heterogeneity of NAFLD implies that it is difficult to manage it as a single entity, and the effects of non-significant amounts of alcohol consumed by NAFLD patients on hepatic steatosis have not yet been clearly defined.2 The diagnosis of MAFLD requires radiological evidence of hepatic steatosis and the presence of any one of the following three conditions: overweight/obesity, presence of diabetes mellitus, or evidence of metabolic dysregulation.2 In fact, in their algorithm, the diagnosis of MAFLD is essentially identical to the diagnosis of NAFLD.
There are several problems with this approach. First, putting ‘non’ in the nomenclature of a disease and approaching it through exclusion has been a time-tested, simple and very effective approach in medical science. Non-Hodgkin’s lymphoma and non-small cell carcinoma are prime examples of this approach.98–100 It is indeed peculiar the way the change in name is sought to be justified. The proponents of MAFLD have surprisingly split “nonalcoholic” into two words: ‘non’ and ‘alcoholic’, followed by the assertion that the word “non” trivializes their problem, while the word alcoholic demeans the patient and blames the patient for the disease. This rationale for change in terminology, however, trivializes the seriousness of changing a term which has stood the test of time for almost half a century. Quite to the contrary, the term ‘nonalcoholic’ destigmatizes the patient. The term “metabolic” in MAFLD as a reference to MS itself trivializes the gamut of evidence garnered in NAFLD research to date.
To put things in perspective, the Rome Foundation has been frequently changing the names of functional bowel disorders, many of which are not so functional after all. For example, in a validation study of 1,452 patients with gastrointestinal symptoms, the Rome III criteria performed only modestly in identifying those with functional dyspepsia and were not significantly superior to previous definitions.101 Despite one of the rationales for the revision being to allow separation of functional dyspepsia and gastroesophageal reflux disease more clearly, almost identical proportions of patients meeting criteria for each of the different definitions of FD were found to have erosive esophagitis.101
Second, merely replacing the term NAFLD with MAFLD would not make the entity any less heterogeneous. At the moment, their exists considerable uncertainty regarding the pathogenesis of NAFLD, and a change in name cannot be justified.
Third, the impact of nonsignificant intake of alcohol on hepatic metabolism is itself very unclear; some studies have shown a decreased progression to NASH with moderate alcohol consumption, as acknowledged in the consensus paper. Moreover, metabolic complications in alcoholic fatty liver disease have been demonstrated too.102 Besides, lipid metabolism abnormalities,103 disturbances in sirtuin104 and PPAR-γ105 pathways have also been shown to occur in alcoholic liver disease. Can the change in terminology to MAFLD provide adequate answers to these perplexing questions? Thus, it is clear that the reasons stated for such a sudden change are very flimsy and have no rational basis.
Interestingly, in a review concerning the challenges of the diagnosis and classification of NAFLD by Hashimoto, Tokushige and Ludwig in 2015, it was argued that recommendations to change the nomenclature of NAFLD to metabolic fatty liver or metabolic steatohepatitis would be of little help, and since patients with NAFLD/NASH were also being treated by cardiologists and diabetologists in addition to hepatologists, such changes in nomenclature would create confusion and should be avoided.106
It will be worthwhile to mention here that as regards the change in nomenclature, European Liver Patients Association (ELPA) had expressed its concerns to the European Commission in 2018, arguing for a change in nomenclature.1 We tried to elicit an answer from ELPA in this regard - if this was true and if so, the reasons for such a suggestion. We also sought to know how this was decided, the percentage of patients who feel uncomfortable with such terminology and importantly, if the heterogeneity in NAFLD pathogenesis—especially in non-Caucasians—was taken into account. However, despite repeated queries, unfortunately, we did not receive any reply from ELPA.
Most of the emerging literature on the NAFLD versus MAFLD debate have pooled patients of NAFLD with other patients of fatty liver due to dual etiology and then compared these patients with NAFLD patients.107 This has obviously resulted in increased prevalence of hepatic fibrosis in this cohort108 and it needs no rocket science to understand this, since fatty liver patients with dual etiology including alcohol (up to 60 gram/day) have been compared to patients with NAFLD! Instead of achieving ‘homogeneity’ which the proponents of MAFLD harp on, this has paradoxically made the entity more heterogenous. Besides, another offshoot of this change would be that this will push the field back, since all study protocols to date have been based on NAFLD. It would not be possible to reconcile previous data on NAFLD with new data on MAFLD.